LAG-3 作为第三个检查点抑制剂。
LAG-3 as the third checkpoint inhibitor.
机构信息
Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
出版信息
Nat Immunol. 2023 Sep;24(9):1415-1422. doi: 10.1038/s41590-023-01569-z. Epub 2023 Jul 24.
Lymphocyte activation gene 3 (LAG-3) is an inhibitory receptor that is highly expressed by exhausted T cells. LAG-3 is a promising immunotherapeutic target, with more than 20 LAG-3-targeting therapeutics in clinical trials and a fixed-dose combination of anti-LAG-3 and anti-PD-1 now approved to treat unresectable or metastatic melanoma. Although LAG-3 is widely recognized as a potent inhibitory receptor, important questions regarding its biology and mechanism of action remain. In this Perspective, we focus on gaps in the understanding of LAG-3 biology and discuss the five biggest topics of current debate and focus regarding LAG-3, including its ligands, signaling and mechanism of action, its cell-specific functions, its importance in different disease settings, and the development of novel therapeutics.
淋巴细胞激活基因 3（LAG-3）是一种高表达于耗竭 T 细胞的抑制性受体。LAG-3 是一种很有前途的免疫治疗靶点，目前有超过 20 种针对 LAG-3 的治疗药物正在临床试验中，一种固定剂量的抗 LAG-3 和抗 PD-1 药物组合已被批准用于治疗不可切除或转移性黑色素瘤。尽管 LAG-3 被广泛认为是一种有效的抑制性受体，但关于其生物学和作用机制仍存在一些重要问题。在本观点中，我们重点关注对 LAG-3 生物学理解的差距，并讨论当前关于 LAG-3 的五个最大争议和关注的话题，包括其配体、信号转导和作用机制、细胞特异性功能、在不同疾病环境中的重要性以及新型治疗药物的开发。
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